Most of the primary tumors, such as breast cancer, lung cancer, gastric cancer, esophageal cancer, thyroid cancer, cervical cancer, ovarian cancer, colorectal adenocarcinoma, pancreatic cancer and laryngeal cancer, generally metastasize by lymph nodes. Therefore, lymph node staging plays an important role not only in determining the therapeutic regimens and prognosis for most of the primary tumors, but also in accurately evaluating the extent of preoperative lymph node metastasis in clinic. However, the available probes (e.g., ICG) and imaging methods (e.g., PET/CT, magnetic resonance imaging and ultrasound) for detecting lymphatic metastasis in clinic fail to effectively recognize a normal lymph node from a lymph node with tumor metastasis. Moreover, the systematic lymphadenectomy will result in a large trauma and a higher occurrence of postoperative sequelae. It is more serious that some patients suffering from early cancer may passively undergo unnecessary lymphadenectomy treatment due to the failure in determining the status of lymph nodes. Given the above, if the status of the lymph node metastasis can be detected preoperatively and intraoperatively, the involving area of the tumor will be accurately determined, thereby greatly reducing the patient's pain and improving the life quality.
Molecular imaging is a tool by which the normal or pathological intracellular molecular process can be studied in vivo so as to the physiological and pathological changes in organisms at the molecular or cellular level, providing a new technique for in vivo monitoring of disease processes, in vivo tracing of gene therapy, evaluation of in vivo efficacy and research of law of in-vivo activity of functional molecules. This technique has the advantages of non-invasion, real-time and in-vivo monitoring, fine imaging, and high sensitivity and specificity. There are various imaging methods used in the molecular imaging to image the specific target in vivo and the core part is the design of molecular probes. Molecular imaging methods mainly include radionuclide imaging, magnetic resonance imaging, optical imaging, ultrasonic imaging and photoacoustic imaging, and each imaging modal has respective advantages and limitations. For example, the fluorescence imaging has advantages of high sensitivity, relatively low cost and simple operation, but its penetration depth is limited. The radionuclide imaging and the magnetic resonance imaging have no limitation on the penetration depth, but they respectively have the defects of low spatial resolution and low sensitivity. In addition, the information acquired by a single imaging modal is too limited to reflect the complexity and specificity of organisms. Therefore, the combination of multiple molecular imaging modals and the construction of a multi-modal molecular probe, which are complementary to each other, can provide more accurate and reliable imaging information for biomedical research.
Fluorescent conjugated polymer, as a fluorescent probe, has unique photophysical and photochemical properties. It has been first reported by Swager et al. from MIT in 1995 that the fluorescent conjugated polymer can amplify the fluorescence signal by hundreds of times due to a π-π* conjugated molecular wire structure, which contributes to the wide application of the fluorescent conjugated polymer in the detection of biomacromolecules such as nucleic acids and proteins, and biological micromolecules such as ATP and glucose. Moreover, due to the presence of π-π* conjugated molecular wire structure, the fluorescent conjugated polymer has some advantages over the conventional small-molecule fluorescent compounds, for example, (1) the fluorescent conjugated polymer has a better stability; (2) the electronic structure and the fluorescence emission wavelength of the conjugated polymer can be adjusted by changing and modifying the chemical structure; and (3) in the premise of not changing the binding constant, the response signal may be amplified by hundreds of times to improve the sensitivity of the detection. In addition, compared to the semiconductor quantum dots, the fluorescent conjugated polymer is free of any toxic metals, allowing for less toxicity. Thus, the fluorescent conjugated polymer has recently been considered as a desired tool to be applied in the molecular imaging. However, the light emitted by the reported fluorescent conjugated polymer nanomaterials is mainly visible light, so that these materials are not very suitable for the in vivo imaging of small animals. Furthermore, fluorescent conjugated polymer nanoprobe-based targeted imaging has also not been reported to be used in the detection of lymph node metastasis.
Therefore, there is an urgent need for those skilled in the art to develop a conjugated polymer nanoprobe and a preparation method thereof for multi-modal molecular imaging, benefiting the targeted imaging of the lymph node metastasis and the differentiation between a normal lymph node and a lymph node with tumor metastasis.